6n3y | pdb_00006n3y

Human Histidine Triad Nucleotide Binding Protein 1 (Hint1) with Bound 5'-O-[(3-Indolyl)-1-Ethyl]Carbamoyl Guanosine

spinqualitylabelsall models 6n3y, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6n3y is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, HHJ Gene: HINT1, HINT, PKCI1, PRKCNH1 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HINT1_HUMAN] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity). Publication Abstract from PubMed The interactions between the mu-opioid (MOR) and N-methyl-d-aspartate receptor (NMDAR) constitute an area of intense investigation because of their contributions to maladaptive neuroplasticity. Recent evidence suggests that their association requires the involvement of histidine triad nucleotide-binding protein (HINT1) with the enzyme's active site being critical in its regulatory role. Since it is known that spinal blockade of NMDA receptors prevents the development of opioid analgesic tolerance, we hypothesized that spinal inhibition of the HINT1 enzyme may similarly inhibit opioid tolerance. To address these questions, we evaluated novel HINT1 active-site inhibitors in two models of NMDAR and MOR interaction, namely, MOR inhibition of spinal NMDA activation and acute endomorphin-2 tolerance. These studies revealed that while the tryptamine carbamate of guanosine inhibitor, TrpGc, blocked both the development of opioid tolerance and the inhibitory effect of opioids on NMDA activation of the NMDA receptor, acyl-sulfamate analogues could only block the latter. Thermodynamic binding and X-ray crystallographic studies suggested that there are key differences between the bound HINT1-inhibitor surfaces that may be responsible for their differential ability to probe the ability of HINT1 to regulate cross talk between the mu-opioid receptor and NMDA receptor in the spinal cord. Inhibition of HINT1 Modulates Spinal Nociception and NMDA Evoked Behavior in Mice.,Shah RM, Peterson C, Strom A, Dillenburg M, Finzel B, Kitto KF, Fairbanks C, Wilcox G, Wagner CR ACS Chem Neurosci. 2019 Oct 16;10(10):4385-4393. doi:, 10.1021/acschemneuro.9b00432. Epub 2019 Sep 25. PMID:31503445 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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